Cystic fibrosis (CF) is characterized in the respiratory tract by chronic hyper-secretion of mucus and chronic infection, especially with a virulent mucoid strain of P. aeruginosa. Surprisingly, interactions between products elaborated by these micro-organisms and secretory cells of the airways have not been elucidated. We will test the hypothesis that certain strains of mucoid P. aeruginosa which chronically infect the respiratory tract in CF elaborate a product that further stimulates mucin secretion by airway cells, thereby exacerbating the airway obstruction characteristic of CF and leading to more extensive infection. This "vicious cycle" could be a major factor in the pathogenesis of CF in the lung. In preliminary studies, we have observed that cell-free filtrates from cultures of mucoid P. aeruginosa obtained from the respiratory tracts of CF patients increased mucin secretion by rodent tracheal tissue in short-term organ culture. This effect was not mimicked by filtrates from non-mucoid strains of P. aeruginosa isolated from the same CF patients. This proposal is designed to assess the significance of these observations for CF patients. The relationship between this mucin secretion-stimulating activity and the disease state and clinical condition of the patient of origin will be studied. In addition, those strains having stimulatory activity will be characterized as to serotype and mucoidy of colonies. The cellular biology of the interaction between Pseudomonas filtrates and airway secretory cells in rodent and human fetal tissues will be examined by biochemical, histochemical and ultrastructural means. Preliminary biochemical characterization and separation of the "active" substance in the filtrates also will be carried out.